Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection

Darintr Sosothikul; Panya Seksarn; Sureeporn Pongsewalak; Usa Thisyakorn; Jeanne Lusher

doi:10.1160/TH06-02-0094

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 627-634
DOI: 10.1160/TH06-02-0094

Wound Healing and Inflammation/Infection

Schattauer GmbH

Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection

Authors

Darintr Sosothikul

¹Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
Panya Seksarn

¹Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
Sureeporn Pongsewalak

¹Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
Usa Thisyakorn

¹Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
Jeanne Lusher

²Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA

Abstract

Summary

Dengue virus causes a febrile illness: Dengue fever (DF), and less frequently a life-threatening illness: Dengue hemorrhagic fever (DHF). Although severe bleeding remains a major cause of death in DHF, the pathogenesis of bleeding is poorly understood. This prospective cohort study was designed to determine the extent of activation of endothelial cells and the hemostatic system in correlation with clinical severity, and also to detect the best prognostic factor(s) for DHF. Endothelial cell activation, coagulation, anticoagulant and fibrinolysis parameters were measured in 42 children with Dengue infections (20 with DF and 22 with DHF) during three phases of illness. In DHF patients, during the febrile phase, vonWillebrand factor antigen (vWF:Ag),tissue factor (TF) and plasminogen activator inhibitor (PAI-1) were significantly elevated, while platelet counts andADAMTS 13 (a disintegrin and metalloprotease with thrombospondin repeats) were significantly low compared to DF patients. During the toxic phase, soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA) and PAI-1 were also significantly increased, while ADAMTS 13 and thrombin activatable fibrinolysis inhibitor (TAFIa) were significantly low compared to DF patients. Abnormal vWF multimers were seen only in DHF patients. For endothelial cell injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, increased antifibrinolytic factors and consumption of natural anticoagulants, each appeared to play an important role in the development of hemorrhage in Dengue patients. Using logistic regression analysis, we found plasma VWF:Ag to be the best indicator of progression to DHF.

Keywords

ADAMS/ADAMTS 13 - hemostasis - Dengue virus infection - endothelial cell

Full Text

References

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